Regulation of Herbal and Traditional Medicines in Germany BfArM in Dialogue - TradReg 2017 Prof. Dr. Werner Knöss, Dr. Jacqueline Wiesner TradReg2017 Germany September 2017 Page 1
Federal Institute for Drugs and Medical Devices (BfArM) BfArM; Bonn; Germany TradReg2017 Germany September 2017 Page 2
Medicinal Product Supervision Administration Federal Level AMG Laender Level Paul-Ehrlich- Institut - marketing authorisations - dossier-related inspections - pharmacovigilance inspections - pharmacovigilance management - management of product defects (Rapid Alert System) - OMCL (PEI, vaccines) OMCLs - GMP/GCP inspections - GMP/GDP certificates - manufacturers/importers authorisations - export certificates - drug testing ZLG Inspectorates TradReg2017 Germany September 2017 Page 3
TradReg2017 Germany September 2017 Page 4
European Union political union of 28 Member States about 500 Mio inhabitants 24 official languages TradReg2017 Germany September 2017 Page 5
Key Institutions European Commission European Parliament Regulatory Framework, Law Directives, Regulations National authorities Assessment Marketing Authorisation DCP, MRP, national European Pharmacopeia Quality standards General Herbal Drugs/Preparations EMA Coordination Guidance Centralised Procedure TradReg2017 Germany September 2017 Page 6
Pharmacopoeia Network and Cooperation DAB Pharmacopoeia ( 55 Drug Law) HAB Transfer / Implementation * European Pharmacopoeia (Ph. Eur.) TradReg2017 Germany September 2017 Page 7
Herbal and Traditional Medicines in Germany Particular Environment phytotherapy, homeopathy, anthroposophy long history of usage science, research, education regulation in the pharmaceutical legal framework acceptance among citizens 25% of European market small- and medium-sized German enterprises TradReg2017 Germany September 2017 Page 8
Specific Expertise in Division 4 responsibility for about 10.000 finished medicinal products about 35% combination products herbal medicinal products, traditional herbal medicinal products, homeopathic medicinal products, anthroposophic medicinal products, vitamins, minerals, water, traditional medicines assessment, life cycle options and limitation scientific advice advice to the Federal Ministery of Health TradReg2017 Germany September 2017 Page 9
Traditional Medicines in Germany - Basic Figures 2000 herbal medicinal products (23% combinations) 1700 licensed herbal medicinal products (15% combinations) 300 registered traditional herbal medicinal products (40% combinations) 1350 licensed homeopathic medicinal products (86%) 1050 licensed anthroposophic medicinal products (62%) 3900 registered homeopathic and anthroposophic (48%) medicinal products TradReg2017 Germany September 2017 Page 10
Specific Division for Traditional Medicines at BfArM Licensing 4 Prof. Dr. W. Knöss Complementary Medicines and Traditional Medicines Unit 41 Project Management Unit 42 Herbal and traditional medicinal products 29% 6% 3% 3% 31% physicians pharmacists food chemists Unit 43 Homeopathic and anthroposophic medicinal products 29% biologists chemists biopharmacologists Unit 44 Cannabis Agency TradReg2017 Germany September 2017 Page 11
Establishment of the Cannabis Agency Single Convention on Narcotic Drugs, 1961 (United Nations): shall establish a governmental agency to control cultivation and supply of Medical Cannabis Gesetz zur Änderung betäubungsmittelrechtlicher und anderer Vorschriften (10th March 2017) Der Anbau von Cannabis zu medizinischen Zwecken unterliegt der Kontrolle des BfArM. Dieses übernimmt die Aufgaben einer staatlichen Stelle Cannabis Agency TradReg2017 Germany September 2017 Page 12
Strategy on regulation of Medical Cannabis - key elements and objectives Patients with severe illness Reimbursement Improved access Pharmaceutical quality (DAB) Prescription by doctors Future perspective: More marketing authorisations TradReg2017 Germany September 2017 Page 13
European and Global Activities of Division Licensing 4 Active contribution to the European network substantial resources, substantial contributions harmonisation in the EU (EMA; HMA; EDQM) numerous rapporteurships; RMS Chairperson Committee on Herbal Medicinal Products (HMPC, EMA) until 2016 coordination national authorities EMA EDQM Global contacts and communication e.g. IRCH-meetings (WHO) GIZ project Bilateral contacts, conferences, training, education TradReg2017 Germany September 2017 Page 14
Old standards New standards Harmonised standard United in diversity TradReg2017 Germany September 2017 Page 15
Pharmaceutical Legislation in the EU Directive 2001/83/EC ( Basic regulation on medicinal products) amended by Directive 2003/63/EC (Annex I; CTD criteria) Directive 2004/24/EC (THMP) Quality Basic approach: Assessment of Safety Efficacy TradReg2017 Germany September 2017 Page 16
Pharmaceutical Legislation in the EU Definitions: Medicinal product Herbal medicinal product Traditional herbal medicinal product (longstanding tradition, plausibility) Herbal substance (Eur. Ph. Herbal drug ) Herbal preparation (Eur. Ph. Herbal drug preparation ) TradReg2017 Germany September 2017 Page 17
Access to the Market Options and Concepts Marketing authorisation - Full application (e.g. new medicinal products) [Article 8 of Directive 2001/83/EU] - Well-established use [Article 10a of Directive 2001/83/EU] Registration - Traditional use [Article 16a of Directive 2001/83/EU] TradReg2017 Germany September 2017 Page 18
Recent new Herbal Medicinal Products in the EU based on a Full Application TradReg2017 Germany September 2017 Page 19
Tasks EMA HMPC Monographs Safety + Efficacy Guidelines Standards European Pharmacopeia Eur. Ph. Monographs Quality National authorities or EMA (centralised) Product Applications Assessment Licensing TradReg2017 Germany September 2017 Page 20
Marketing Authorisation Registration Pharmacovigilance Consumer information; labeling; advertising new trials new tests Efficacy Safety bibliographicc bibliographic Quality Control traditional use bibliographic new tests Good Manufacturing Practice Good Agricultural and Collection Practice applies to registered and to authorised HMP may be replaced by a monograph or the list from the HMPC in registrations (WEU/TRAD) identical for marketing authorisations and registrations new well-established traditional TradReg2017 Germany September 2017 Page 21
First Registration of a Traditional Herbal Medicinal Product in Europe Legislation 2004 December 2005: Traditional registration Continuous access to the market Combination (n=13) Quality guideline conform Plausibility Additional data TradReg2017 Germany September 2017 Page 22
Monographs - Contributions of BfArM (source: EMA) TradReg2017 Germany September 2017 Page 23
Specific Division for Traditional Medicines at BfArM Licensing 4 Prof. Dr. W. Knöss Complementary Medicines and Traditional Medicines Unit 41 Project Management Unit 42 Herbal and traditional medicinal products 29% 6% 3% 3% 31% physicians pharmacists food chemists Unit 43 Homeopathic and anthroposophic medicinal products 29% biologists chemists biopharmacologists Unit 44 Cannabis Agency TradReg2017 Germany September 2017 Page 24
Homeopathy a Traditional Therapeutic System Samuel Christian Hahnemann (1755 1843) Essay on a New Principle for Ascertaining the Curative Powers of Drugs (1796) Germany and France Medicinal Products Act (1976) Scientific pluralism in medical therapy Regulation as Medicinal Products TradReg2017 Germany September 2017 Page 25
Regulatory Approach in Germany Integration of homeopathic and anthroposophic medicines in the regulatory framework for medicines Evaluation of medicinal products before access to the market Unit with special expertise at BfArM Consideration of particular characteristics in assessment of quality, safety and efficacy Protection of patients - risks - fraudulent products / claims/ information Expert committees - Commission C anthroposophic medicinal products - Commission D homeopathic medicinal products TradReg2017 Germany September 2017 Page 26
Medicinal Products Act - Germany Section 4 Definitions of additional terms 26) A homeopathic medicinal product is any medicinal product prepared in accordance with a homeopathic manufacturing procedure described in the European Pharmacopoeia or, in the absence thereof, in the pharmacopoeias currently used officially in the EU Member States. TradReg2017 Germany September 2017 Page 27
National Procedures Registration ( 38 f) Without any indication claim Mandatory labelling: Homeopathic Medicinal product without approved therapeutic indication Consult a doctor if symptoms persist during the use of the medicinal product Marketing authorisation ( 21 ff ) With indication claim Instead of results of pharmacological and toxicological tests and of clinical trials other scientific documents may be presented.. Furthermore, the medical experience gained by the specific schools of therapy must also be taken into consideration. TradReg2017 Germany September 2017 Page 28
Quality reproducibility by process Homeopathic medicinal products are characterised by the homeopathic manufacturing procedure and specifications Raw materials and dosage forms have to comply with the requirements of the GHP and Ph. Eur. TradReg2017 Germany September 2017 Page 29
Safety Regulatory strategy by BfArM (Germany) Common regulatory standards for safety evaluation No compromise Consideration of particulars Lack of data Regulatory responsibility Publication of concept Buchholzer et al., 2014. Regulatory Toxicology and Pharmacology 68, 193 200 Current concepts on integrative safety assessment of active substances of botanical, mineral or chemical origin in homeopathic medicinal products within the European regulatory framework. TradReg2017 Germany September 2017 Page 30
European Network - HMPWG Forum for exchange of regulatory and scientific expertise Guidance on assessment for national authories Non-clinical safety (safe dilution grade) (art. 14(1) of Dir. 2001/83/EC) Advice and expertise on procedural, regulatory and scientific issues Guidance on registration to applicants TradReg2017 Germany September 2017 Page 31
BfArM: Dialogue and solutions Examples Scientific advice (scientific, clear, target-oriented) BfArM in Dialogue Meetings with associations Viscum Pyrrolizidine alkaloids Virus validation in homeopathy Interactions TradReg2017 Germany September 2017 Page 32
Dialogue and solutions Strategy of BfArM (Germany) Clear commitment on regulation of herbal and traditional medicines Allocation of resources to the European network and global initiatives Availability of medicinal products and public health Consideration of particulars Science-based decision making within legal framework Regulatory responsibility for options and limitations TradReg2017 Germany September 2017 Page 33
Thank you very much for your attention! Contact Federal Institute for Drugs and Medical Devices Division Complementary and Traditional Medicinal Products Kurt-Georg-Kiesinger-Allee 3 D-53175 Bonn Contact person Prof. Dr. Werner Knöss werner.knoess@bfarm.de www.bfarm.de Tel. +49 (0)228 99 307-5638 Fax +49 (0)228 99 307-5395 TradReg2017 Germany September 2017 Page 34